Fungal Cil'lWlics illlli Biolog,· 21. 1,-2'1 11 qq" :\ni('h' :'\(L FGH,< I Supplied by U. S. Dept. of Agric., National Center for Agricultural Utilization Research, Peoria, IL REVIEW Metabolic Pathway Gene Clusters in Filamentous Fungi Nancy P. Keller* and Thomas M. Hohnt * Department of Plant Pathology and Microbiology. Texas A&M University. College Station. Texas 77843-2132: and tMycotoxin Research Unit. National Center for Agricultural Utilization Research. USDAIARS. Peoria. Illinois 61604 Accepted for publication February 7. 1997 7711 Keller, N. P., and Hohn, T. M. 1997. Metabolic pathway gene clusters in filamentous fungi. Fungal Genetics and Biology 21 ,17-29. ;: 1997 Academic Press Index Descriptors: Aspergillus nidulans; filamentous fungi; gene clusters; metabolic. Clusters of functionally' related genes are a general feature of prokaryotic gene organization but are much less prevalent in eukaryotes. The discovery that genes for certain types of metabolic pathways are clustered in filamentous fungi is relatively recent. Only 8 years ago in a discussion of the proline utilization pathway genes, Hull et al. (1989) commented that "The organization and regula- tion of the genes involved in L-proline catabolism in the ascomycete fungus Aspergillus nidulalls are of particular interest because, rather unusually for functionally related eukaryotic genes. they are all clustered." This view was supported by studies of metabolic pathway gene linkage relationships from a variety of eukaryotes. Although ge- netic e\idence was available suggesting that some meta- bolic pathway genes were closely linked in A Ilidulalls (see Clutterbuck 1992), recognition of gene clustering as an important feature of fungal metabolic pathways had to await the molecular characterization of specific pathways. Fungal gene clusters can be broadly defined as the close linkage of two or more genes that participate in a common metabolic or developmental pathway. Fungi possess numer- ous pathways for what can be described as "dispensable" metabolic functions. and research over the last 5 veal's has 1087,1845/97 $25.00 Copyright 1997 by Academic Press All rights of reproduction in any form reserved. shO\\11 that the genes for these dispensable pathways are often organized in gene clusters. The term dispensable metabolic pathways is used here to describe pathways that either are not required for gro\\th or are onl;' reqUired for gro\\th under a limited range of conditions. Dispensable metabolic pathways are typically e:-.pressed under subopti- mal grO\\th conditions and most likeI;' function to enhance fungal survival in response to nutrient deprivation or competing organisms. In this re\iew. two major t;1)es of dispensable metabolic pathways \\ill be discussed. cata- bolic pathways for the utilization of low-molecular-weight nutrients such as proline or quinate (nutrient utilization pathways) and biosYllthetic pathways for low-molecular- weight compounds which include antibiotics and mycotox- ins (natural product pathways). Nutrient utilization pathways increase the metabolic versatilit;, of filamentous fungi. enabling them to utilize a variety of complex compounds as alternative sources of nutrients. E:-.pression of the appropriate catabolic path- ways can be critically important for sunival under limiting nutrient gro\\th conditions. However, many of these nutri- ents are not commonly' encountered by fungi. so there is little benefit derived from e:-.pressingpathway genes consti- tutively To ensure that the reqUired catabolic pathways are expressed appropriately in response to changing nutri- tional conditions while Simultaneously limiting the loss of cellular resources due to unnecessary pathway gene e:-.pres- sion. fungi have developed complex regulatory systems. To date. enzymatic and regulatory genes for four well-studied dispensable catabolic pathways (quinate, ethanol, proline. 17